Certain salicyloylamino acids have been demonstrated as being useful in the delivery of active agents, particularly, through the oral route. See, for example, U.S. patent application Ser. No. 08/414,654, now U.S. Pat. No. 5,650,386, filed Mar. 31, 1995, now U.S. Pat. No. 5,650,386.
Two methods of preparation of such compounds are illustrated in U.S. patent application Ser. No. 08/414,654, now U.S. Pat. No. 5,650,386, filed Mar. 31, 1995 and provisional U.S. patent application Ser. No. 60/003,111, filed Sep. 1, 1995, published as WO96/30036, Oct. 3, 1996.
Additionally, Ho et al., Synthetic Communications, 26(14), 2641-2649 (1986) summarizes a number of methods for the preparation of .omega.-aminoalkanoic acids. These methods include the introduction of an amine group by the conversion of a ketone to an oxime or a carboxylate to a nitrile, followed by reduction by azidide opening of an anhydride, followed by Schmidt rearrangement, or by Hoffman rearrangement of an amide with aqueous base and bromine. Boc protected and N-acylated .omega.-amino alkanoic acids can also be obtained by hydrolysis of the N-Boc and N-acylated lactams, respectively. Ho et al. presents an additional synthetic route to N-Boc protected or Boc-amino acid coupled with .omega.-aminoalkanoic acids.
However, there is still a need for an efficient, economical, and commercially practical method for the preparation of salicyloylamino acids.